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Pharmacokinetics of peptide T in patients with Acquired Immunodeficiency Syndrome (AIDS) |
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| Authors: | Michael R. Ruff Craig Smith Tim Kingan Howard Jaffe Peter Heseltine Mark A. Gill Kenneth Mayer Candace B. Pert T. Peter Bridge |
| Affiliation: | 1 Integra Institute, Potomac, MD,, U.S.A. 2 Intramural Research Program, National Institute of Mental Health, Bethesda, MD, U.S.A. 3 Peptide Design, Germantown, MD, U.S.A. 4 Department of Internal Medicine Los Angeles County Medical Center, University of Southern California, Los Angeles, U.S.A. 5 Department of Pharmacology, Los Angeles County Medical Center, University of Southern California, Los Angeles, U.S.A. f Fenway Community Health Center, Boston, MA 02115, USA a Brown University, Providence, RI, U.S.A. |
| Abstract: | 1. The pharmacokinetics of Dalal-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiecy disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intraveneous (i.v.) or intranasal (i.n.), via metered sprayer, administration. 2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearence rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA. 3. Bioavailabilty, determined for a 2 mg test dose in six individuals was 9.3 ± 6.9 nmol/L. Peak plasma levels of 41 ± 30 nmol/L after 10 mg i.n., 2.8 ± 5.9 nmol/L after 2mg i.n., and 0.13 ± 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months. |
| Keywords: | AIDS antiviral human peptide T pharmacokinetics therapeutic |
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